Ahmedabad tolerance induction protocol and chronic renal allograft dysfunction: pathologic observations and clinical implications

• Published in: Diagnostic pathology Vol. 4; no. 1; p. 4
• Main Authors: Patel, Rashmi D, Vanikar, Aruna V, Aziz, Feroz A, Shah, Pankaj R, Trivedi, Hargovind L
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30.01.2009; BioMed Central; BMC
• Subjects: Diagnosis; Graft rejection; Health aspects; Immune response; Kidneys; Patient outcomes; Prevention; Risk factors; Study Protocol; Transplantation; India
• ISSN: 1746-1596; 1746-1596
• DOI: 10.1186/1746-1596-4-4

Chronic Renal Allograft Dysfunction (CRAD) is responsible for a large number of graft failures. We have abrogated acute T-cell rejections using Ahmedabad Tolerance Induction Protocol (ATIP) with hematopoietic stem cell transplantation (HSCT) under non-myeloablative conditioning pre-transplant. However B-cell mediated rejections and CRAD continue to haunt us. We carried out retrospective analysis of renal allograft biopsies performed in the last 4 years to evaluate the effect of ATIP on CRAD. Biopsies diagnosed as per modified Banff criteria belonged to 2 groups: ATIP under low dose immunosuppression of cyclosporine/Azathioprine/Mycofenolate mofetil+ Prednisolone, subjected to donor leucocyte transfusion, anti-T/B cell antibodies, low dose target specific irradiation, cyclophosphamide, cyclosporin followed by HSCT pre-transplant; controls who opted out of ATIP were transplanted under standard triple drug immunosuppression. Demographics of both groups were comparable. Incidence of chronic changes was higher in controls (17.5%) vs. 10.98% in ATIP over a mean follow up of 151.9 months in the former and 130.9 months in the latter. Proteinuria and hypertension were higher in controls (48.4%) vs. ATIP (32.7%) with chronic transplant glomerulopathy, focal global sclerosis in 67.7% in controls vs. 46.7% in ATIP, acute on chronic T/B cell rejection in 51.6% controls vs. 28.1% ATIP, with peritubular capillary C4d deposits in 19.4% controls vs. 1.9% ATIP biopsies. Acute on chronic calcineurin inhibitor toxicity was higher in ATIP (71.9%) vs. 48.4% in controls. Chronic immune injury was less with ATIP vs controls as compared to a higher incidence of chronic calcineurin inhibitor toxicity in the former.